The present invention relates to a novel method for producing lactogenesis in nonpregnant dairy animals.
It is known that prolactin, a hormone produced by the anterior lobe of the pituitary gland, is an essential factor in initiating and sustaining lactation in mammals, and that its action depends upon the presence of other essential hormones such as estrogens, progesterone and oxytocin.
In 1971, there was described the use of 17.beta.-estradiol and progesterone to induce lactation in nonpregnant dairy cows, wherein subcutaneous injections were administered twice daily of 17.beta. estradiol (0.1 mg/kg body weight per day), and progesterone (0.25 mg/kg body weight per day), during a period of 1 to 7 days; Smith et al., J. Dairy Sci., 54:1886 (1971). While successful lactation occurred in some cows with this treatment, a substantial number of animals failed to lactate or produced only a very limited amount of milk. It is possible that the failure of the nonlactating group might have been the absence of prolactin as a component of the lactogenic complex, since it is known that serum prolactin levels increase dramatically approximately 2 days prepartum in pregnant dairy animals; Convey, J. Dairy Sci., 57: 905-917 (1974).
The availability of prolactin per se is so limited that its use for potentiating hormonal induction of lactation in dairy animals is impractical. However, a number of other compounds such as prostaglandins, thyrotropin releasing hormone (TRH), serotonin and many psychoactive drugs stimulate prolactin release: Clemens and Meites, Lactogenic Hormones, pp. 111-142 (1974); Louis et al., Proc. Soc. Exp. Biol. Med. 147: 128-133 (1974); Tucker et al., ibid, 149: 462-469 (1975). Most of these compounds either result in a prolactin release lasting only a few minutes or cause the release of both prolactin and thyroxine, which latter substance may inhibit the lactogenic role of prolactin.
The use of reserpine, an ester alkaloid derived from the roots of Rauwolfia serpentina, to induce lactation in pregnant animals via prolactin release is known. Thus reserpine injections produce prolonged release of prolactin in rats and rabbits: Kanematsu et al., Proc. Soc. Ex. Biol. Med., 113: 967-974 (1963); Meites, ibid., 96: 728-731 (1957); Meites et al., ibid. 101: 563-565 (1959).
Bass et al., Arch. int. de Pharmacodynamie et de Therapie, 211: 188-192 (1974) studied the effect of administering various known prolactin releasers, including reserpine, to lactating ewes during the fourth month of lactation when milk yield has fallen to less than 50%, thus indicating lack of endogenous prolactin. Of 14 compounds tested, only five yielded a significant increase in milk yield during treatment (6 days) which faded when injections were stopped, and reserpine was not among these five. The reserpine was found to produce a syndrome including diarrhoea, loss of appetite, and prostration.
The oral administration of reserpine and analogous substances derived from Rauwolfia plants, to livestock, poultry, pigs and the like, by inclusion in animal feeds is disclosed in U.S. Pat. No. 3,092,496, where Rauwolfia root is said to be a growth stimulant, and in U.S. Pat. No. 3,178,340 for its tranquilizing effect.